The objective of the present research is to determine the net effect of chronic administration of the antidepressant drugs, desipramine and iprindole, on the functional activity of the locus coeruleus (LC)-hippocampal system. Chronic treatment with either desipramine or iprindole resulted in a significant increase in the firing rate of those hippocampal cells that were suppressed by LC stimulation. This finding suggests that long-term administration of these antidepressants is antagonistic to the tonic phase of the functioning of the LC-hippocampal system. The effect of the drugs on he phasic aspect of the functioning of the system was studied by examining the efficacy of noradrenergic nerve impulse to affect both hippocampal and LC cells. We have found that long-term treatment with iprindole reduced the capacity of noradrenergic nerve impulse to induce hippocampal suppression. A suppression of both the tonic and phasic phases of the functioning of the LC-hippocampal system by chronic antidepressant treatment would suggest that the net effect of these drugs is antagonistic to the system.